AU2007204550A1 - Pharmaceutical compounds that contain nanoparticles useful for treating restenotic lesions - Google Patents
Pharmaceutical compounds that contain nanoparticles useful for treating restenotic lesions Download PDFInfo
- Publication number
- AU2007204550A1 AU2007204550A1 AU2007204550A AU2007204550A AU2007204550A1 AU 2007204550 A1 AU2007204550 A1 AU 2007204550A1 AU 2007204550 A AU2007204550 A AU 2007204550A AU 2007204550 A AU2007204550 A AU 2007204550A AU 2007204550 A1 AU2007204550 A1 AU 2007204550A1
- Authority
- AU
- Australia
- Prior art keywords
- nanoparticles
- analogues
- pharmaceutical compounds
- rapamycin
- restenotic lesions
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Description
WO 2007/079560 PCT/BR2007/000015 1 PHARMACEUTICAL COMPOUNDS THAT CONTAIN NANOPARTICLES USEFUL FOR TREATING RESTENOTIC LESIONS FIELD OF INVENTION The present invention refers to pharmaceutical compounds that contain nanoparticles useful for treating restenotic lesions. More specifically, it comprises pharmaceutical compounds that contain nanoparticles, nanocapsules, liposomes, or nanotubes and one or more cellular antiproliferative active agents with or without cationic coating for treating restenotic lesions. BACKGROUND OF INVENTION Development of restenosis can be angiographically observed and defined as a reduction of the coronary luminal diameter that happens after the dilatation of an obstruction. In order to avoid the closing of the vessel, metallic tubular devices known as stents are implanted. This technique widely reduces restenosis problem, but it does not stop it from existing. Blood flow ends up damaged due to a new obstruction of coronary artery after stent implant occurred by unordered and excessive proliferation of flat endothelial and muscle cells inside stent. Thus, restenosis occurs in approximately 25% of cases of stent implant not coated with medication, such rate can raise up to 50%, according to patient's clinic and angiographic characteristics of obstructive lesion and coronary artery to be treated. Recent studies have shown that restenosis rate may be significantly reduced by stent implant coated with drugs capable to inhibit neointimal proliferation for some weeks. Although such stents reduce restenosis to 8%, which is the smallest rate already reached by a therapeutical device in coronary artery, restenosis persists and constitutes a serious and difficult problem to find solution. Moreover, the high cost of stent coated with medicine limits its regular use in most countries. Several techniques were employed for treating intrastent restenosis like angioplasty with balloon catheter, cutting-balloon, directional atherectomy and laser. All these techniques present high cost, high complexity and do not present results better than balloon catheter, which is the simplest and cheapest option. Braquitherapy with beta and gamma radiation was also much studied as a technique for treatment of restenotic lesions. Initial results were very promising, but a loss of the initial result was observed over time, which gives to this technique a palliative effect.
WO 2007/079560 PCT/BR2007/000015 2 Other negative aspects of this technique are very high cost and logistics, because there is the need of a braquitherapy specialist during the procedure and short-period radioactive sources besides protection and insulation of areas in the case of use of gamma radiation. Therefore, currently, braquitherapy is a nearly extinct technique. Use of stent coated with antiproliferative medicine constitutes the best therapeutic strategy today to treat restenotic lesions with recurrence index between 14 and 22%. But, high cost and the results not so satisfactory such as those presented with use of these drug coated stent in treatment of de novo lesions, that are virgin of treatment lesions, limit the wide employment of this therapeutic strategy. Administration of rapamycin orally was also studied and presented a rate of restenosis of approximately 22% with the use of high doses. Costs are reasonable, but results are not so satisfactory. Rapamycin or sirolimus is a strong antiproliferative cell agent that acts on phase G1 S of cell cycle. It also has antibiotic, antifungal and immunosuppressive properties. As antiproliferative cell agent it has been used in coronary stents, providing significant reduction of neointimal intrastent hiperproliferation rates named restenosis. This antiproliferative cell effect was shown in several in vitro studies and in animals and humans. Technical literature presents products and methods, which, despite reducing the rate of new intrastent restenosis, do not present satisfactory medium- and long-term results. So, there also is the need for the development of a method that presents better results such as local infusion of nanoparticles that contain one or more antiproliferative cell medicine with or without cationic coating. Thus, technical literature neither describe nor suggest medicine compounds that contain nanoparticles at least one active cell antiproliferative agent such as rapamycin (sirolimus) or analogues and paclitaxel or analogues, with or without cationic coating for treating restenotic lesions. Such compounds are being descried and claimed in the present application. SUMMARY Generally, the present invention refers to medicine compounds that contain nanoparticles useful for treatment of restenotic lesions, and comprise nanoparticles of rapamycin (sirolimus) or analogues and/or nanoparticles of paclitaxel or analogues, alone or together with mentioned nanoparticles, with or without cationic coating.
WO 2007/079560 PCT/BR2007/000015 3 It is a characteristic of the invention, nanoparticles that contain one or more antiproliferative cell agents for local infusion for treating intrastent restenotic lesions. It is a characteristic of the invention, a method of administration of rapamycin or analogues and/or paclitaxel and analogues, alone or together that constitute a lower cost of the procedure when compared with other techniques for restenosis treatment. It is a characteristic of the invention, a method of simple execution. DETAILED DESCRIPTION OF INVENTION Nanoparticles useful for treatment of restenotic lesions, the object of the present invention, comprise nanoparticles of rapamycin (sirolimus) or analogues or nanoparticles of paclitaxel or analogues, alone or together, said nanoparticles with or without cationic coating. Cationic coating aims to increase the adhesion, penetration and diffusion of nanoparticles that contains at least one antiproliferative cell medicine in the tissue responsible for neointimal hyperplasia as cells have negative electrical power and nanoparticles are positively charged. Optionally, nanocapsules, liposomes or nanotubes are employed. Solution with nanoparticles of rapamycin or analogues is infused in a dose that comprises interval from 10 to 500 Ug/cm 2 of stent surface preferably from 80 to 240 Ug/cm 2 of stent surface. Analogues of rapamycin (sirolimus) are: Biolimus, Everolimus, Zotarolimus and Mitomycin. Analogues of paclitaxel comprise docetaxel. Method consists of infusion of nanoparticles of rapamycin or analogues and/or paclitaxel or analogues alone or together, on the coronary artery's wall through a catheter specific for local medicine infusion. Such procedure must be done after stent dilatation with conventional balloon catheter. Local infusion of nanoparticles that contains one or more antiproliferative cell agents constitutes a therapeutic strategy, technically of simple technical execution, potentially efficient and economically viable for treating restenotic intrastent lesions. In order to evaluate results obtained from these compounds in restenotic lesions treatment, it was performed a study in swine as it follows. Two solutions of nanoparticles containing rapamycin in bioabsorbable polymer were prepared. One solution with and the other without cationic coating.
WO 2007/079560 PCT/BR2007/000015 4 Twelve commercially available stents measuring 3.0 x 16.0mm were implanted at high pressure in the left anterior descendent coronary artery (2.75mm of diameter) in six swine, wherein two stents were implanted by coronary artery one in the transition of the proximal third for medium and another in the medium third. In 30 days all swine were studied with cineangiocoronariography and intracoronary ultrasound, that showed evident restenosis (obstruction superior to 50%) in all previously implanted stents. Next, an angioplasty with conventional balloon catheter measuring 3.0x16.0mm in all the stents was performed followed by local infusion of nanoparticles of rapamycin without cationic coating with medicine infusion catheter in four stents and nanoparticles with cationic coating in other four. In 60 days, all swine were studied with cineangiocoronariography and intracoronary ultrasound that showed stenosis with average area of 63% in stents treated only with conventional angioplasty, 20% in stents treated with nanoparticles of rapamycin without cationic coating and 18% in stents treated with nanoparticles of rapamycin with cationic coating. Obtained results have shown satisfactory effect of local infusion of nanoparticles of rapamycin with and without cationic coating in the prevention of recurrent episodes of restenosis after intrastent restenosis treatment. There is no significant difference in the use of nanoparticles of rapamycin with cationic coating in relation to nanoparticles of rapamycin without cationic coating, but it is verified a small advantage favoring nanoparticles with cationic coating.
Claims (6)
1. PHARMACEUTICAL COMPOUNDS THAT CONTAIN NANOPARTICLES USEFUL FOR TREATING RESTENOTIC LESIONS characterized for comprising nanoparticles of rapamycin (sirolimus) or analogues and/or nanoparticles of paclitaxel or analogues alone or together, mentioned nanoparticles with cationic coating.
2. PHARMACEUTICAL COMPOUNDS THAT CONTAIN NANOPARTICLES USEFUL FOR TREATING RESTENOTIC LESIONS characterized for comprising nanoparticles of rapamycin (sirolimus) or analogues and/or nanoparticles of paclitaxel or analogues alone or together, mentioned nanoparticles without cationic coating.
3. PHARMACEUTICAL COMPOUNDS THAT CONTAIN NANOPARTICLES USEFUL FOR TREATING RESTENOTIC LESIONS according to claims 1 and 2, characterized for optionally nanocapsules, liposomes, nanotubes being employed.
4. PHARMACEUTICAL COMPOUNDS THAT CONTAIN NANOPARTICLES USEFUL FOR TREATING RESTENOTIC LESIONS according to claims 1 and 2, characterized by the fact that analogues of rapamycin are selected from Biolimus, Everolimus, Zotarolimus and Mitomycin.4
5. PHARMACEUTICAL COMPOUNDS THAT CONTAIN NANOPARTICLES USEFUL FOR TREATING RESTENOTIC LESIONS according to claims 1 and 2, characterized by the fact that analogous of paclitaxel comprise docetaxel.
6. PHARMACEUTICAL COMPOUNDS THAT CONTAIN NANOPARTICLES USEFUL FOR TREATING RESTENOTIC LESIONS characterized for comprising infusion of nanoparticles of rapamycin or analogues and/or paclitaxel or analogues alone or together, on the coronary artery's wall through a catheter specific for local medicine infusion.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BRC10600285-4A BRPI0600285C1 (en) | 2006-01-13 | 2006-01-13 | nanoparticulate pharmaceutical compounds useful for treating restenosis |
BRPI0600285-4 | 2006-01-13 | ||
PCT/BR2007/000015 WO2007079560A2 (en) | 2006-01-13 | 2007-01-12 | Pharmaceutical compounds that contain nanoparticles useful for treating restenotic lesions |
Publications (1)
Publication Number | Publication Date |
---|---|
AU2007204550A1 true AU2007204550A1 (en) | 2007-07-19 |
Family
ID=38256650
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU2007204550A Abandoned AU2007204550A1 (en) | 2006-01-13 | 2007-01-12 | Pharmaceutical compounds that contain nanoparticles useful for treating restenotic lesions |
Country Status (8)
Country | Link |
---|---|
US (1) | US20090011005A1 (en) |
EP (1) | EP1978957A4 (en) |
JP (1) | JP2009523133A (en) |
CN (1) | CN101365447A (en) |
AU (1) | AU2007204550A1 (en) |
BR (1) | BRPI0600285C1 (en) |
CA (1) | CA2636336A1 (en) |
WO (1) | WO2007079560A2 (en) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8998846B2 (en) | 2006-11-20 | 2015-04-07 | Lutonix, Inc. | Drug releasing coatings for balloon catheters |
US20080276935A1 (en) | 2006-11-20 | 2008-11-13 | Lixiao Wang | Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs |
EP2066321A2 (en) * | 2006-11-20 | 2009-06-10 | Lutonix, Inc. | Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs |
US9700704B2 (en) | 2006-11-20 | 2017-07-11 | Lutonix, Inc. | Drug releasing coatings for balloon catheters |
US8414525B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8414910B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US9737640B2 (en) | 2006-11-20 | 2017-08-22 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8414909B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8414526B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids |
US8425459B2 (en) | 2006-11-20 | 2013-04-23 | Lutonix, Inc. | Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent |
WO2010024898A2 (en) | 2008-08-29 | 2010-03-04 | Lutonix, Inc. | Methods and apparatuses for coating balloon catheters |
CN102970990A (en) | 2010-05-03 | 2013-03-13 | 帝国制药美国公司 | Non-aqueous taxane pro-emulsion formulations and methods of making and using the same |
KR101314579B1 (en) * | 2011-04-07 | 2013-10-10 | 광주과학기술원 | Paclitaxel- loaded polymeric nanoparticle and preparation thereof |
JO3685B1 (en) | 2012-10-01 | 2020-08-27 | Teikoku Pharma Usa Inc | Non-aqueous taxane nanodispersion formulations and methods of using the same |
HUP1400075A2 (en) | 2014-02-14 | 2015-08-28 | Druggability Technologies Ip Holdco Jersey Ltd | Complexes of sirolimus and its derivatives, process for the preparation thereof and pharmaceutical composition containing them |
CN114028623B (en) * | 2021-10-26 | 2024-02-27 | 江苏朴芃医疗科技有限公司 | Cardiac shunt |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6537579B1 (en) * | 1993-02-22 | 2003-03-25 | American Bioscience, Inc. | Compositions and methods for administration of pharmacologically active compounds |
US6273913B1 (en) * | 1997-04-18 | 2001-08-14 | Cordis Corporation | Modified stent useful for delivery of drugs along stent strut |
US20030199425A1 (en) * | 1997-06-27 | 2003-10-23 | Desai Neil P. | Compositions and methods for treatment of hyperplasia |
US20030129215A1 (en) * | 1998-09-24 | 2003-07-10 | T-Ram, Inc. | Medical devices containing rapamycin analogs |
EA200001109A1 (en) * | 1998-05-20 | 2001-06-25 | ДЗЕ ЛИПОСОМ КОМПАНИ, Инк. | NEW PARTICLES, COMPOSITION ON THEIR BASIS AND METHOD OF TREATMENT WITH THEIR APPLICATION |
US8067032B2 (en) * | 2000-12-22 | 2011-11-29 | Baxter International Inc. | Method for preparing submicron particles of antineoplastic agents |
US20030065382A1 (en) * | 2001-10-02 | 2003-04-03 | Fischell Robert E. | Means and method for the treatment of coronary artery obstructions |
US20050095267A1 (en) * | 2002-12-04 | 2005-05-05 | Todd Campbell | Nanoparticle-based controlled release polymer coatings for medical implants |
CN102697737B (en) * | 2003-04-03 | 2014-03-19 | 杰西.L.-S.奥 | Tumor-targeting drug-loaded particles |
KR20060012628A (en) * | 2003-05-19 | 2006-02-08 | 백스터 인터내셔널 인코포레이티드 | Solid particles comprising an anticonvulsant or an immunosuppressive coated with one or more surface modifiers |
US8043631B2 (en) * | 2004-04-02 | 2011-10-25 | Au Jessie L S | Tumor targeting drug-loaded particles |
EP1768692B8 (en) * | 2004-07-01 | 2015-06-17 | Yale University | Targeted and high density drug loaded polymeric materials |
US7727554B2 (en) * | 2004-12-21 | 2010-06-01 | Board Of Regents Of The University Of Nebraska By And Behalf Of The University Of Nebraska Medical Center | Sustained-release nanoparticle compositions and methods for using the same |
WO2006102378A2 (en) * | 2005-03-21 | 2006-09-28 | Macusight, Inc. | Drug delivery systems for treatment of diseases or conditions |
-
2006
- 2006-01-13 BR BRC10600285-4A patent/BRPI0600285C1/en active Search and Examination
-
2007
- 2007-01-12 EP EP07701600A patent/EP1978957A4/en not_active Withdrawn
- 2007-01-12 CA CA002636336A patent/CA2636336A1/en not_active Abandoned
- 2007-01-12 JP JP2008549721A patent/JP2009523133A/en active Pending
- 2007-01-12 WO PCT/BR2007/000015 patent/WO2007079560A2/en active Application Filing
- 2007-01-12 CN CNA2007800017443A patent/CN101365447A/en active Pending
- 2007-01-12 AU AU2007204550A patent/AU2007204550A1/en not_active Abandoned
-
2008
- 2008-07-01 US US12/217,028 patent/US20090011005A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP1978957A2 (en) | 2008-10-15 |
WO2007079560A3 (en) | 2007-12-27 |
BRPI0600285A (en) | 2007-10-02 |
CN101365447A (en) | 2009-02-11 |
JP2009523133A (en) | 2009-06-18 |
WO2007079560A2 (en) | 2007-07-19 |
US20090011005A1 (en) | 2009-01-08 |
EP1978957A4 (en) | 2013-01-09 |
BRPI0600285C1 (en) | 2011-10-11 |
CA2636336A1 (en) | 2007-07-19 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |